RT Journal Article
SR Electronic
T1 Vitamin D enhances responses to interferon-β in MS
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e622
DO 10.1212/NXI.0000000000000622
VO 6
IS 6
A1 Feng, Xuan
A1 Wang, Zhe
A1 Howlett-Prieto, Quentin
A1 Einhorn, Nathan
A1 Causevic, Suad
A1 Reder, Anthony T.
YR 2019
UL http://nn.neurology.org/content/6/6/e622.abstract
AB Objective To determine the effect of vitamin D3 on interferon-β (IFN-β) response and immune regulation in MS mononuclear cells (MNCs).Methods MNCs from 126 subjects, including therapy-naive patients with different forms of MS, plus patients with MS receiving IFN-β or glatiramer treatment, plus healthy controls were incubated in vitro with IFN-β-1b ± vitamin D3 (calcitriol). Activation of the IFN-β–induced transcription factor, p-Y-STAT1, and antiviral myxovirus A (MxA) protein was measured with flow cytometry and Western blots; serum proteins were measured with a customized 31-protein multiplex assay.Results Vitamin D enhanced in vitro IFN responses, as measured by induction of p-Y-STAT1 and MxA in MNCs, T cells, and monocytes. Vitamin D augmentation of IFN responses was seen in untreated and in IFN-β-1b–treated MS. The combination of vitamin D plus IFN-β reduced Th1 and Th17 cytokines, and increased Th2 responses, reversing the effect of IFN-β alone. Exacerbations and progression in untreated patients reduced the vitamin D enhancement of IFN responses. Vitamin D had less effect on IFN response in clinically stable glatiramer-treated than in IFN-β–treated patients.Conclusion Vitamin D enhances IFN-β induction of multiple proteins and also reverses the Th1/Th2 bias in MS seen with IFN-β alone. The combination of vitamin D and IFN-β has potential benefit in ameliorating MS.BDNF=brain-derived neurotrophic factor; ConA=concanavalin A; EAE=experimental autoimmune/allergic encephalomyelitis; GA=glatiramer acetate; HC=healthy control; HGF=hepatocyte growth factor; IFN-β=interferon-β; LIF=leukemia inhibitory factor; MFI=median fluorescence intensity; MNC=mononuclear cell; MxA=myxovirus A; NGF=nerve growth factor; PMA=phorbol myristate acetate; PMS=progressive MS; PPMS=primary progressive MS; RRMS=relapsing/remitting MS; RRMS-a=active RRMS; RRMS-s=stable RRMS; SPMS=secondary progressive MS; TPO=thymopoietin; VDR=vitamin D receptor; VDSI=Vitamin D Stimulation Index